1. Che-1 Promotes Tumor Cell Survival by Sustaining Mutant p53 Transcription and Inhibiting DNA Damage Response Activation
- Author
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Claudio Passananti, Agata Desantis, Simona Iezzi, Francesca La Rosa, Maurizio Fanciulli, Alfonso Bellacosa, Gianluca Bossi, Giovanni Blandino, Aristide Floridi, Annapaola Franchitto, Silvia Di Agostino, Sergio Galanti, Barbara Benassi, Cristina Sorino, Francesca De Nicola, and Tiziana Bruno
- Subjects
Cancer Research ,DNA Repair ,Transcription, Genetic ,DNA damage ,Cell Survival ,Mutant ,Transplantation, Heterologous ,RNA polymerase II ,Apoptosis ,Breast Neoplasms ,CELLCYCLE ,Biology ,Transactivation ,Mice ,Transcription (biology) ,Cell Line, Tumor ,Animals ,Humans ,RNA, Small Interfering ,Tumor Suppressor Proteins ,Nuclear Proteins ,Tumor Protein p73 ,Cell Biology ,Cell cycle ,G2-M DNA damage checkpoint ,DNA-Binding Proteins ,Repressor Proteins ,Oncology ,Cancer research ,biology.protein ,Tumor Suppressor Protein p53 ,Apoptosis Regulatory Proteins ,DNA Damage - Abstract
Summary Che-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription and, in response to DNA damage, promotes p53 transcription. In this study, we investigated whether Che-1 regulates mutant p53 expression. We found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and that Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo. Notably, loss of Che-1 activates DNA damage checkpoint response and induces transactivation of p73. Therefore, these findings underline the important role that Che-1 has in survival of cells expressing mutant p53.
- Published
- 2010
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